An mtDNA mutation, 14453G -> A, in the NADH dehydrogenase subunit 6 associated with severe MELAS syndrome

We report a novel point mutation in the gene for the mitochondrially encode d ND6 subunit of the NADH:ubiquinone oxidoreductase (complex I of the respi ratory chain) in a patient with MELAS syndrome. The mutation causes a chang e from alanine to valine in the most conserved region of the ND6 subunit. T he patient was heteroplasmic for the mutation in both muscle and blood, but the mutation was not detected in the patient's mother. A marked reduction of complex I activity was found in the patient's muscular tissue. This is t he first report of a mutation in the ND6 subunit causing MELAS. Our data co nfirm the genetic heterogeneity in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, and confirms that MELAS can be caused by mutation in polypeptide-coding mtDNA genes.